Bone implants are in great demand for the treatment of for victims of trauma, military actions, congenital and degenerative diseases, as well as sports- and age-related injuries. The need for replacement tissue far outweighs the availability of donor tissue. The deficit is further exacerbated by war injuries. In this project we will target engineering of artificial bone implants that can potentially provide an endless supply of the bone material and eliminate the risk of immune rejection or disease transfer. Borrowing the concept from Nature, we propose to take advantage of multi-scale design of the bone scaffolds spanning the scale from 10-8 to 10-1 m. Multiple requirements of the artificial bone tissue, that include both mechanical and biological properties, make this approach acutely necessary. The following Specific Aims will be pursued to produce and implant prototype sustaining rapid development of bone cells, as well as high compression strengths. (1). Preparation of a biodegradable nanocomposite of PLGA and calcium phosphate (CP) nanoparticles with improved mechanical properties (10-8-10-6 m scale); (2). Construction of 3D biodegradable scaffold structure with inverted colloidal crystal (ICC) topography (10-4-10-6 m scale). (3) Increased cell attachment and growth by optimizing surface roughness through the application of nanoparticles to the scaffold surface (10-8-10-4 m scale); (4). Preparation of ICC scaffolds from PLGA-CP composite with a computer-designed cross-bar geometry (10-3-10-1 m scale); and (5). In vivo testing of the integrated scaffold with optimal geometry, mechanical properties, and surface roughness. These Specific Aims will allow us to obtain prototypes of implantable scaffolds, identify potential challenges and prove or disprove the principal concept of multi-scale design for artificial bone. [unreadable] [unreadable] [unreadable]